Neonatal jaundice caused by hyperbilirubinemia affects more than 50% of all newborn children. Significantly elevated levels of bilirubin are neurotoxic and can cause a permanent neurological condition called kernicterus. Evidence that lower levels of bilirubin may lead to subtle neurological injury exists, but despite extensive research on the subject, it has not been possible to precisely define a "safe" level of hyperbilirubinemia for some infants;i.e., a level that does not require phototherapy or blood transfusion. Whether subtle neurological effects are transient is also an open question for many bilirubin-associated conditions. One reason for difficulty determining safe levels of serum bilirubin is that many concurrent conditions are known to affect bilirubin's ability to cross the blood brain barrier. Another problem is that traditional measurements of serum bilirubin evaluate free and albumin-bound bilirubin levels together. It is only free bilirubin that can cross the blood brain barrier. In this study we will measure free and total bilirubin in a cohort of full term, healthy infants with neonatal jaundice. Results will be compared with steady state VEP measurements of threshold and response amplitudes for contrast, grating, and vernier acuity. Tests will be performed longitudinally at 6 and 12 months of age to learn whether any effects are transient, worsen, or remain the same. Control infants with low levels of serum bilirubin will also be examined. Preliminary data from our lab indicates that signal responses are diminished in infants with neonatal jaundice, and that in the case of vernier acuity, thresholds worsen with increasing total serum bilirubin levels. These effects persist to at least 9 months of age, even though jaundice dissipates in the first few weeks of life. Total and free bilirubin will be compared to VEP findings to learn which is more accurate for predicting VEP changes. If findings from this study suggest a deleterious effect of bilirubin on the visual system, then this could lead to additional studies that could have a significant impact on the care of newborn children. Findings of no effect will also be significant and offer additional evidence that current management guidelines can't be improved. Determining which bilirubin measurement is most accurate could also influence future care of newborn infants. PUBLIC HEALTH RELEVANCE: Neonatal jaundice, caused by elevated bilirubin levels, affects more than 50% of full term infants;yet precise guidelines for its treatment are debated. Using a new approach to measure the type of bilirubin that can cause neurological damage, and an assay that quantitates vision later in infancy, we will explore whether neonatal jaundice has an enduring negative effect on the visual system. If we find a detrimental effect, this will lead to further studies, and could have an enormous impact on the health of children. If no effect is found, this, too, is important and offers reassurance that current guidelines for management of jaundice are correct.